This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Related articles in Am J Pathol Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Albinger-Hegyi, A. Articles by Zimmermann, D. R. Search for Related Content PubMed PubMed Citation Articles by Albinger-Hegyi, A. Articles by Zimmermann, D. R.

(American Journal of Pathology. 2002;160:823-832.)
© 2002 American Society for Investigative Pathology

Technical Advance

High Frequency of t(14;18)-Translocation Breakpoints Outside of Major Breakpoint and Minor Cluster Regions in Follicular Lymphomas

Improved Polymerase Chain Reaction Protocols for Their Detection

From the Laboratory of Molecular Biology, Institute of ClinicalPathology, Department of Pathology, University Hospital,Zürich, Switzerland

The detection of t(14;18) translocations is widely used for the diagnosis and monitoring of follicular lymphomas displaying a high prevalence for this aberration. Cytogenetics, Southern blotting, and polymerase chain reaction (PCR) are commonly used techniques. It is generally believed that the vast majority of the breakpoints occurs on chromosome 18 in the major breakpoint region (mbr) and the minor cluster region (mcr). Yet, by improving long-distance PCR protocols we identified half of the breakpoints outside of these clusters. Our study included biopsies from 59 patients with follicular lymphoma. Seventy-one percent carried translocations detectable with our long-distance PCR protocol. The novel primer sets were derived from the hitherto uncharacterized 25-kb-long stretch between mbr and mcr that we have sequenced for this purpose. Sequence analysis of the novel breakpoints reveals a wide distribution between mbr and mcr displaying some clustering 16 kb downstream from the BCL2 gene. By including a primer for this intermediate cluster region in standard PCRs we could also improve the detection of t(14;18) translocations in formalin-fixed and paraffin-embedded biopsies. Our new PCRs are highly sensitive, easy to perform, and thus well suited for routine analysis of t(14;18) translocations for the primary diagnosis of follicular lymphoma and surveillance of minimal residual disease.

Related articles in Am J Pathol:

The Role of Genetic Instability in Tumor Growth: Challenge of a Concept

Am J Pathol 2002 160: 753-754. [Full Text]  

This article has been cited by other articles:

				C. M. McHale, Q. Lan, C. Corso, G. Li, L. Zhang, R. Vermeulen, J. D. Curry, M. Shen, R. Turakulov, R. Higuchi, et al. Chromosome Translocations in Workers Exposed to Benzene J Natl Cancer Inst Monographs, July 1, 2008; 2008(39): 74 - 77. [Abstract] [Full Text] [PDF]

				O. K. Weinberg, W. Z. Ai, M. R. Mariappan, C. Shum, R. Levy, and D. A. Arber ''Minor'' BCL2 Breakpoints in Follicular Lymphoma: Frequency and Correlation with Grade and Disease Presentation in 236 Cases J. Mol. Diagn., September 1, 2007; 9(4): 530 - 537. [Abstract] [Full Text] [PDF]

				M. A Catherwood, D. Gonzalez, C. Patton, E. Dobbin, L. Venkatraman, and H D. Alexander Improved clonality assessment in germinal centre/post-germinal centre non-Hodgkin's lymphomas with high rates of somatic hypermutation J. Clin. Pathol., May 1, 2007; 60(5): 524 - 528. [Abstract] [Full Text] [PDF]

				L Venkatraman, M A Catherwood, A Patterson, T F Lioe, W G McCluggage, and N H Anderson Role of polymerase chain reaction and immunocytochemistry in the cytological assessment of lymphoid proliferations J. Clin. Pathol., November 1, 2006; 59(11): 1160 - 1165. [Abstract] [Full Text] [PDF]

				P J Batstone and J R Goodlad Efficacy of screening the intermediate cluster region of the bcl2 gene in follicular lymphomas by PCR J. Clin. Pathol., January 1, 2005; 58(1): 81 - 82. [Abstract] [Full Text] [PDF]

				S. C. Raghavan, S. Houston, B. G. Hegde, R. Langen, I. S. Haworth, and M. R. Lieber Stability and Strand Asymmetry in the Non-B DNA Structure at the bcl-2 Major Breakpoint Region J. Biol. Chem., October 29, 2004; 279(44): 46213 - 46225. [Abstract] [Full Text] [PDF]

				S. Roulland, P. Lebailly, Y. Lecluse, M. Briand, D. Pottier, and P. Gauduchon Characterization of the t(14;18) BCL2-IGH Translocation in Farmers Occupationally Exposed to Pesticides Cancer Res., March 15, 2004; 64(6): 2264 - 2269. [Abstract] [Full Text] [PDF]

				S. L. Barrans, P. A.S. Evans, S. J.M. O'Connor, R. G. Owen, G. J. Morgan, and A. S. Jack The Detection of t(14;18) in Archival Lymph Nodes: Development of a Fluorescence in Situ Hybridization (FISH)-Based Method and Evaluation by Comparison with Polymerase Chain Reaction J. Mol. Diagn., August 1, 2003; 5(3): 168 - 175. [Abstract] [Full Text] [PDF]

				M. Sanchez-Beato, A. Sanchez-Aguilera, and M. A. Piris Cell cycle deregulation in B-cell lymphomas Blood, February 15, 2003; 101(4): 1220 - 1235. [Abstract] [Full Text] [PDF]

				J. J. Biagi and J. F. Seymour Insights into the molecular pathogenesis of follicular lymphoma arising from analysis of geographic variation Blood, May 29, 2002; 99(12): 4265 - 4275. [Abstract] [Full Text] [PDF]

				J. C. Aster and J. A. Longtine Detection of BCL2 Rearrangements in Follicular Lymphoma Am. J. Pathol., March 1, 2002; 160(3): 759 - 763. [Abstract] [Full Text] [PDF]